tbuckley/cabot-search huggingface dataset:
PB1737: OUTCOME OF ACUTE LYMPHOBLASTIC LEUKEMIA IN INFANTS AT THE NATIONAL CANCER INSTITUTE EGYPT: 10 YEARS’ EXPERIENCE
Authors: Nesreen Ali, Dina Elbadrawy, Mona Elashry, Lobna Shalaby
Journal: HemaSphere (2023)

Topic: 2. Acute lymphoblastic leukemia - Clinical Background: Acute lymphoblastic leukemia (ALL) in infants is known to be biologically different from ALL in older children. Aims: We aimed to determine the frequency, clinical and laboratory characteristics, and outcome of infants with acute lymphoblastic lymphoma treated at the National Cancer Institute (NCI), Cairo University, Egypt. Methods: This is a retrospective study that included infants below the age of 1 year with acute lymphoblastic leukemia who were newly diagnosed during the period from January 2010 to December 2019 and treated at the National Cancer Institute, Cairo University, Egypt. Results: Of total 40 cases, 25 (62.5%) cases were males, and 15 (37.5%) cases were females, 14 (35%) cases were < 6 months old and 26 (65%) cases were ≥ 6 months. TLC at presentation was >250 x103 cells/mm3 in 11 (27.5%) cases. KMT2A rearrangement by FISH was done for 24 (60%) patients. It was wild type in 5 (20%) cases and rearranged in 19 (80%) cases. According to response to steroids, 17 (42.5%) cases were classified as standard risk, and 23 (57.5%) cases as high risk. Only two (5%) patients received steroids before admission to the NCI. Regarding the line of treatment implicated, 24 (60%) cases received Interfant-99, 14 (35%) cases received Saint Jude Total XV, and 2 (5%) died on day 1. Relapse occurred in 10 (25%) patients. At the end of the study, 28 (70%) patients were dead and 12 (30%) were alive. Of the patients who died, 6 (21.4%) died in complete remission, 18 (64.3%) died in induction phase, and 4 (14.3%) died from disease. The most common cause of death among study participants was infection and sepsis in 22 (78%). There was no difference in overall survival (OS) or event-free survival (EFS) between those treated with Interfant-99 versus Saint Jude Total XV, with a p value of 0.924 and 0.340, respectively. For the whole group, three-year OS was 20.2% and three-year EFS was 17.7%. Summary/Conclusion: The survival outcomes of our patients are lower than those of comparable studies conducted in developed countries but quite relevant to those conducted in developing countries. Infection and sepsis, the leading causes of death, account for 78% of deaths, highlighting the importance of supportive care for such a vulnerable group of patients. Keywords: Outcome, Acute lymphoblastic leukemia, Infant
P1669: DIRECT ORAL ANTICOAGULANTS VS LOW MOLECULAR WEIGHT HEPARIN IN THE MANAGEMENT OF PATIENTS WITH PRIMARY OR METASTATIC BRAIN TUMOURS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Wenhui Yu, Jayhan Kherani, Lucy Zhao, Daniel Tham, Allen LI, Harry LI, Ali Eshaghpour, Mark Crowther
Journal: HemaSphere (2023)

Topic: 34. Thrombosis and vascular biology - Biology & Translational Research Background: Patients with primary or metastatic brain tumours are at increased risk of thrombosis like other malignancies. Low-molecular weight heparin (LMWH) is the mainstay of current treatment/prophylaxis. Direct oral anticoagulants (DOACs) are increasingly used for various indications in the population of patients with malignancy. There is limited safety data for patients with primary or metastatic brain tumors as they were excluded from the large trials. Aims: To compare safety and efficacy of DOACs to LMWH in patients with primary and secondary brain tumors. Methods: We conducted a search of MEDLINE and Embase from inception to January 2023. We included randomized and non-randomized cohort studies that compared DOACs to LMWH. Two reviewers screened and extracted data at title/abstract and full-text levels individually and in duplicate. Baseline patient characteristics, details of brain tumour(s), and anticoagulation regimens were extracted. The primary safety outcome was intracranial hemorrhage (ICH). Data was meta-analyzed using random-effects model. Results: Of 287 articles capture in our search, six non-randomized studies (n = 565 patients) were included for analysis. 56% of patients had secondary intracranial tumors with the average duration of anticoagulation being 190 days for DOACs and 200 days for LMWH. There is a trend towards decreased ICH with DOACs as compared to LMWH(OR: 0.55 [95% CI - 0.29,1.07] I2 = 0%) Summary/Conclusion: There is a trend for increased safety of DOACs as compared to LMWH with regards to ICH. Use of DOAC in patients with brain tumours may be favored given their ease of administration. Randomized studies are needed to confirm these findings. Only preliminary analysis has been done thus far. Further planned analysis of these studies includes efficacy outcomes, as well as overall bleeding outcomes. Keywords: Anticoagulation, Oral anticoagulant, Anticoagulants
PB2517: OSTEOMYELITIS IN CHILDREN WITH SICKLE CELL DISEASE: IS MRI PATHOGNOMONIC?
Authors: Murtadha Al Lawati, Zaid Al Hinai, Sameer Raniga, Ahmed Al Kharusi, Ahmed Al Shukaili, Shuwaikha Al Manwari, Yasser Wali, Nawal Al Mashaikhi
Journal: HemaSphere (2023)

Topic: 26. Sickle cell disease Background: Sickle cell disease (SCD) is one of the most common genetic blood disorders in Oman. The incidence of the disease in Oman is around 6% of the population. SCD patients are at high risk to get osteomyelitis (OM). Salmonella species are the most common pathogens for osteomyelitis in SCD compared to staphylococcus aureus in the normal population. The gold standard to diagnose OM is obtaining a positive blood culture and bone/joint biopsy. However, a negative blood culture does not exclude the diagnosis of OM and bone biopsy is an invasive procedure that is not routinely performed for each patient. Standard Magnetic Resonance Imaging (MRI) is a recognized pathognomonic tool in confirming OM in normal populations and has a sensitivity of 100% and specificity of 96%.However, in patients with SCD it is not usually an easy task as patients with significant bone infarcts are difficult to differentiate from bone infections with an MRI sensitivity and specificity of around 82% and 75% respectively in previous reports. Aims: Ambi-directional study done to evaluate the role of clinical, laboratory and radiological parameters in establishing the diagnosis of OM in children with SCD. Methods: Fifty-one SCD patients with a mean age of 9 years were recruited. The inclusion criteria of our study are patients with SCD aged from 6 months to 18 years, both sex, suspected to have OM, and involvement of limb or joint. Clinical, laboratory, and radiological findings were collected and grouped into 2; OM vs VOC patients. Results: In our study, the sensitivity of MRI alone was 29.6% in detecting OM. Cortical destruction was found in only 12.5% of patients who had MRI which confirms the diagnosis of OM. Combined with Clinical and laboratory data the likelihood of diagnosing osteomyelitis increases significantly (image 1). - Definitive OM Erythema & Hotness in the affected limb + Clinical criteria in Possible OMLeukocytosis (>15) with left neutrophilic shiftHigh ESRPositive blood cultureCortical destruction in MRI Possible OM Pain, tenderness & Limited mobility.FeverLeukocytosis (>15) with left neutrophilic shiftSubperiosteal fluid in US > 4mm Unlikely OM Only pain in the affected limb with no other local signs of infectionAbsence of feverNormal WBC countPresence of bone edema, infarction, and subperiosteal edema only without collection Summary/Conclusion: In SCD patients, it is usually difficult to distinguish between OM and VOC. In many cases, the MRI findings were either inconclusive or gave a wrong diagnosis. Combining clinical, laboratory, and radiological data might increase the likelihood of diagnosing OM in these patients. Keywords: Sickle cell disease
PB1831: THE BALANCE BETWEEN STAT3 ISOFORMS AS ESSENTIAL FEATURE IN ACUTE MYELOID LEUKEMIA
Authors: Stefanie Weiss, Anja Holzer, Sophie Edtmayer, Kerstin Fiedler, Bernhard Zdársky, Agnieszka Witalisz-Sieprack, Dagmar Stoiber-Sakaguchi
Journal: HemaSphere (2023)

Topic: 3. Acute myeloid leukemia - Biology & Translational Research Background: The JAK/STAT pathway and its regulation plays an important role in hematologic malignancies. Constitutive activation of STAT3 in leukemic blasts of patients is associated with significantly poorer outcomes. Therefore, STAT3 became an attractive therapeutic target. However, inhibitors of STAT3 have not led to the intended effects. This might be related to the expression ratio of the two alternatively spliced isoforms, the full-length isoform STAT3α and the C-terminally truncated STAT3β. Recently, our research group has shown that STAT3β acts as a tumor suppressor in acute myeloid leukemia (AML). In line, patients with bad prognoses showed a significantly lower STAT3β/α mRNA ratio in leukemic blasts compared to those from patients with good prognoses. In light of these previous findings, the pharmacological induction of a higher STAT3β/α ratio could be a novel therapeutic option in AML. Aims: Due to the fact that a higher STAT3β/α ratio is associated with favorable outcome in AML, the aim of this project is to find drugs that increase the relative level of STAT3β expression without the severe side-effects of traditional therapeutic protocols. The identified drugs will be tested for their anti-leukemic activity in vivo. Methods: To examine the efficiency of candidate drugs in affecting the STAT3 isoform ratio in leukemic cells, we performed in vitro assays such as real-time quantitative PCR and Western blot. Moreover, to control for specificity of the effect on the isoform ratio change we use AML cell lines with STAT3β overexpression or knockout. In addition, we plan to test the anti-leukemic drug activity in vivo, using an MLL/AF9-induced mouse model and xenograft models. Results: We observed that STAT3 isoform expression on protein and mRNA levels can be influenced by drug treatment in different human and murine AML cell lines. Therefore, we want to further analyze the underlying mechanism of these drugs influencing STAT3 isoform expression. Interestingly, we could identify the common antimalaria drug Atovaquone as a potentially attractive candidate. The effect of an increased STAT3β/α ratio is paralleled by the anti-leukemic activity of Atovaquone. Furthermore, we plan to address the anti-leukemic effect of Atovaquone in vivo. Other antimalaria drugs and a structure analogue of Atovaquone had no impact on the expression of the two alternatively spliced STAT3 isoforms. Summary/Conclusion: By comparing different drugs our results demonstrated that Atovaquone positively affects the STAT3β/α ratio in AML cell lines. This could be potentially of therapeutic relevance in AML. Keywords: Acute myeloid leukemia, STAT3
PB1783: UNRAVELING THE TUMOR SUPPRESSIVE ROLE OF STAT3B IN ACUTE MYELOID LEUKEMIA
Authors: Sophie Edtmayer, Agnieszka Witalisz-Siepracka, Bernhard Zdársky, Stefanie Weiss, Kerstin Fiedler, Thomas Eder, Valeria Poli, Florian Grebien, Dagmar Stoiber
Journal: HemaSphere (2023)

Topic: 3. Acute myeloid leukemia - Biology & Translational Research Background: One major mediator of cytokine signaling is the signal transducer and activator of transcription 3 (STAT3). In acute myeloid leukemia (AML) patients STAT3 is frequently found constitutively activated or overexpressed, which is associated with increased proliferation and poorer overall survival. Apart from this, STAT3 exists in two distinct isoforms generated by alternative splicing, the full-length transcript STAT3α and the C-terminally truncated isoform STAT3β. While STAT3 generally is considered as an oncogenic driver in malignant diseases, STAT3β gained attention as a favorable prognostic marker and was shown to regulate gene transcription also in a STAT3α-independent manner. We previously revealed that STAT3β plays a tumor suppressive role in AML and could serve as a prognostic marker. However, the molecular mechanism underlying its protective role are still undiscovered. Aims: This study aims to provide a more comprehensive understanding of the STAT3 isoform-specific impact on AML development and progression. Furthermore, we intend to identify STAT3β-regulated genes that could serve as novel therapeutic targets. Methods: We use in vivo models and in vitro assays in combination with next-generation sequencing approaches to identify molecular mechanisms explaining the tumor suppressive function of STAT3β in AML. Briefly, hematopoietic stem cells were isolated from fetal livers of wildtype and STAT3β-deficient mice and retrovirally transduced with the human fusion-oncogene MLL-AF9. Transformed cells were used to analyze the STAT3 isoform-specific impact on different cellular mechanisms in vitro. Furthermore, the cells were transplanted into immunocompromised animals to explore the leukemic potential. Results: Although we failed to detect any proliferative advantage in vitro, lack of STAT3β in murine AML blasts lead to accelerated disease progression and poorer overall survival in immunocompromised mice. Furthermore, flow cytometry-based analysis of infiltrated blasts revealed that leukemic cells lacking STAT3β are less committed to the myeloid lineage. By performing transcriptome analysis of leukemic cells isolated from organs of diseased animals we identified gene sets relevant for myeloid differentiation regulated by STAT3β. Summary/Conclusion: Understanding the tumor suppressive property of STAT3β on cellular processes is crucial to discover novel therapeutic targets in AML. As a next step, we aim to validate STAT3β-specific targets using ChIP sequencing that might have translational relevance. Keywords: STAT3, Tumor suppressor, AML
PB2292: DEVELOPMENT OF CARDIOTOXICITY NEGATIVELY IMPACTS IN OVERALL SURVIVAL IN PATIENTS WITH LYMPHOMA TREATED WITH FIRST-LINE ANTHRACYCLINES
Authors: Alberto Lopez Garcia, Ester Macia, Sandra Gomez-Talavera, Eva Castillo-Bazan, Daniel Morillo, Borja Ibañez, Raul Cordoba
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Anthracycline-induced cardiotoxicity (CT) is a growing public health problem that will increase over the years because of curative intent with good results of immunochemotherapy regimes, resulting in long survivors. This is especially important in patients with lymphoma, and it is necessary to identify patients at risk in order to develop preventive strategies. Aims: The primary objective was to identify the incidence of CT in patients with NHL or HL treated with frontline anthracyclines. The secondary one was to establish the relationship between CT development and overall survival (OS) in our cohort. Methods: A single-center retrospective cohort study was conducted between 1 January 2017 and 31 December 2019. Follow-up was conducted until 15 February 2023. Medical records of patients with lymphoma treated with frontline anthracyclines were reviewed. Demographic data, cardiovascular risk factors, biomarkers of myocardial damage and echocardiographic information were collected. CT was defined as a composite of heart failure, myocardial infraction, thromboembolism, conduction disturbances and the development of valve disease or cardiomyopathy. Results: A total of 200 patients were included. Patients characteristics are shown in table 1. Median follow-up was 51.83 months (0.76-73.49) The incidence of CT was 17.4 % (35/200) and those patients were older, with a mean age of 65.17 y/o vs 56.77 y/o in the subgroup of patients who did not develop it (p = 0.008). Median time to development of CT was 6.12 months (1.02-52.86). Dyslipidemia (DL) was more frequently found in the group who developed an event (36.84% vs 13.19% p = 0.037), as well as previous cardiovascular disease (61.05% vs 14.02%. p< 0.0001). The mean baseline NT-proBNP levels in the subgroup with cardiovascular events were 456.1 kg/L ± 101.02 and 251.518 kg/L ± 26.22 in those who did not (p = 0.004) and during the follow up. Hemoglobin level, ECOTT, other FRCV and use of cardioprotective drugs didn’t show differences. Development of CT was associated with a worse OS and it increases with the number of risk factors described in our cohort (Figure 1&2) Summary/Conclusion: Early identification of risk factors, as well as individual patient management and the creation of multidisciplinary teams are necessary with the intention of creating tailored treatment and early identification strategiesKeywords: Toxicity, Myocardial infarction, Survival, Lymphoma
PB2327: IS THERE ANY VALUE OF GERIATRIC INDICES IN DIFFUSE LARGE B CELL LYMPHOMA OF THE ELDERLY?
Authors: Dora Dragčević, Tihana Duić, Ana Bojanic, Inga Mandac Smoljanovic, Marin Kursar, Slavko Gašparov, Delfa Radić-Krišto, Slobodanka Kololonić Ostojić, Marko Lucijanic, Vibor Milunovic
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: DLBCL, NOS is the most common lymphoid neoplasm of the elderly curable in around 60% by first line regimen, but the long-term prognosis of these patients needs to be elucidated. Aims: To evaluate geriatric indices with current standard indices in the DLBCL of elderly in order to evaluate long-term prognosis of the elderly patients. Methods: Inclusion criteria were patients 65 years of age or older with DLBCL, NOS treated with curative intent. While using standard indices (IPI, R-IPI, NCCN-IPI), we used G8 questionnaire, Cumulative Illness Rating Scale-Geriatric (CIRS-G) and Charlson Comorbidity Index (CCI) at the time of diagnosis. Primary outcome was overall survival (OS), with secondary being time to progression (TTP). Statistical analysis was performed by MedCalc. Results: 130 patients were included in the analysis. ORR was 88.4% with 81.2% of CRs. After median of follow up being 63 months, during which a total of 22 patients relapsed and 61 patients died. Median OS time was 73 months with median TTP being 116 months. Using the ROC curve analysis defined cut-off points highest Harrel’s C index for OS was NCCN IPI,G8, IPI, CIRS-G, while for TTP it was G8. In multivariate Cox-regression analysis models CR, NCCN-IPI and CIRS-G were predictors of OS while CR, G8 and CIRS-G predictors of TTP. Summary/Conclusion: G8, CIRS-G and CCI themselves showed only modest to weak ability to discriminate prognosis regarding TTP and OS. Nevertheless, when used in combination with achieved response to therapy and NCCN-IPI, they may significantly improve prognostication since G8, CIRS-G and achieving CR were recognized as independent predictors of TTP and CIRS-G, NCCN-IPI and achieving CR were recognized as independent predictors of OS. In conclusion, the full geriatric assessment is warranted in this population. Keywords: Diffuse large B cell lymphoma, Elderly, DLBCL
PB2384: EVALUATION OF NEW MACHINE LEARNING SYSTEMS FOR PROGNOSTICATION BASED ON GENE EXPRESSION SIGNATURES IN MANTLE CELL AND PERIPHERAL T CELL LYMPHOMAS
Authors: Adrian Mosquera-Orgueira, Jose Angel Diaz Arias, Rocio Serrano Martin, Victor Portela Piñeiro, Andres Peleteiro Raindo, Miguel Cid Lopez, Laura Bao Perez, Marta Sonia Gonzalez Perez, Manuel Mateo Perez Encinas, Maximo Francisco Fraga Rodriguez, Juan Carlos Vallejo Llamas, Jose Luis Bello Lopez
Journal: HemaSphere (2023)

Topic: 20. Lymphoma Biology & Translational Research Background: Mantle cell lymphoma (MCL) and peripheral T cell lymphoma (PTC) represent two relatively rare types of aggressive, adult-onset, non Hodgkin’s lymphoma (NHL). MCL is currently treated with rituximab combined with chemotherapy, which frequently involves high doses of cytarabine, followed by an autologous stem cell transplantation (auto-SCT) in younger and fit patients. PTCL represents a very heterogeneous group of lymphomas with adverse prognosis, which are frequently treated with combinations of chemotherapy followed by an auto-SCT. Although recurrent genomic drivers and molecular prognostic factors have been described in both cases, their adoption in the real world is limited by the low frequency of these lymphomas. Recently, we developed 2 new gene expression signatures for diffuse large B-cell lymphoma (LymForest) and follicular lymphoma (Iacobus-FL) which can derive personalized risk scores when interpreted with a machine learning algorithm. Aims: In the present report, we aimed to evaluate the prognostic value of these profiles in MCL and PTCL patients. For this, we evaluated transcriptomic data allocated in the Gene Expression Omnibus produced by two previous projects focused on MCL (Stott et al, 2017) and PTCL (Iqbal et al, 2014) patients. Methods: A random forest model of survival was constructed according to previous specifications (Mosquera et al, 2022), and an out-of-bag estimate was used for optimism adjustment. Predictions were based on results of the cumulative hazard function and the survival function. Results: Our results indicate perfect reproducibility of the LymForest signature in MCL cases, achieving a c-index of 0.721 for overall survival. By dividing patients into 3 equal subgroups of risk, a clear difference in overall survival was observed (Figure 1 A). Moreover, the combination of LymForest and Iacobus-FL signatures achieved a c-index of 0.626 in PTCL patients, confirming a reasonable predictability in this diagnostic entity. Once again, this score could stratify patients into 3 different and balanced sub groups with divergent overall survival (Figure 1 B). Summary/Conclusion: In conclusion, we prove that these prognostic signatures are also applicable to MCL and PTCL patients, thus broadening its applicability and simplifying the molecular tools needed to risk stratify patients with aggressive lymphomas. Its standardization and evaluation in the context of innovative therapeutic schemes is envisaged.Keywords: Risk factor, Mantle cell lymphoma, Gene expression profile, Peripheral T-cell lymphoma
PB2388: ALTERATIONS OF THE GUT MICROBIOTA AS A NON-INVASIVE DIAGNOSTIC BIOMARKER FOR NATURAL KILLER/T-CELL LYMPHOMA
Authors: Zhuangzhuang Shi, Guoru Hu, Zhaoming LI, Wei-Hua Chen, Mingzhi Zhang
Journal: HemaSphere (2023)

Topic: 20. Lymphoma Biology & Translational Research Background: Natural killer/T cell lymphoma (NKTCL) is a rare lymphoma subtype of peripheral T/NK-cell lymphoma with highly aggressive behavior and poor prognosis. Moreover, it exhibits a predilection for the nasal cavity and upper aerodigestive tract (UAT), which is often mistaken for reactive disease processes, such as chronic rhinosinusitis (CRS). Notably, gut microbiota represents a promising non-invasive diagnostic biomarker for a broad suit of diseases. However, the signatures of gut microflora in NKTCL patients have never been reported, and there is still a wide gap in our understanding of the gut microbiota-derived discriminative strategy for this disease. Aims: To reveal the gut microbial features of NKTCL and highlight the potential diagnostic utility of gut microbiota-derived model. Methods: We recruited 30 NKTCL patients, 28 CRS patients, and 20 healthy controls (HCs) during May 2019 to April 2021, and their fresh feces were collected, to highlight the features of the gut microbiota via metagenomic sequencing in NKTCL patients and its potential role in the early identification of the disease. Results: We found that the alpha diversity was gradually decreased from the HC group to the CRS group to the NKT group although it was not statistically significant, whereas the beta diversity was remarkably increased in NKTCL compared with those of CRS and HCs. In addition, an array of microbial taxa had been identified using the LEfSe method. Most importantly, based on the selected species, a random forest machine learning algorithm was applied to search for a highly fitting model discriminating the UAT-NKTCL from the CRS and HC groups, which achieved better diagnostic utilities. Summary/Conclusion: Altogether, this study shed light on the maladjusted gut microbiota profiles of NKTCL patients for the first time, which indicates a promising non-invasive early diagnostic strategy for the disease. Keywords: Lymphoma